Johanna Bendell, MD: So, outside of the clinical data, because we’re waiting for the trials to be done, what’s your gestalt, John, on chemotherapy and then on radiation therapy—just completely off of study?

John Marshall, MD: For adjuvant?

Johanna Bendell, MD: For neoadjuvant borderline resectable cancer.

John Marshall, MD: I think the sentiment out there that I can sense is a little bit what Caio was saying. It’s sort of a FOLFIRINOX approach just to see if you can get it down and see if you can convert them. There is this hope and a prayer sense that you can convert them, and I’m not against that approach because we do see, every now and then, dramatic responses. We do in-depth shrinking, local-control kind of approaches. I’ve got patients on both kinds of regimens, but a front-line chemotherapy is appropriate. If they’re still unresectable, I lean toward consolidative radiation at that point. I’m a capecitabine junky. So, I treat my patients with it and then they take that forever.

But that’s my approach, generally. And just because I think the ongoing pressure of systemic chemotherapy is hard to maintain in those patients, where you do still have localized disease, it feels right to me to do radiation in that window. It’s often SBRT (stereotactic body radiation therapy), and it’s a short course. Again, I don’t know that that’s the right thing to do. There’s literature on both sides, but that’s where I am.

Johanna Bendell, MD: That sounds about right. If you don’t get there with chemotherapy, keep pushing the envelope to try to get there. George, do you have a thought on which chemotherapy you would use?

George Kim, MD: In the neoadjuvant setting, I think Abraxane-gemcitabine is very reasonable. There’s good data out there, a high 80% range, where it appears to go on to surgery. If you give somebody FOLFIRINOX in the neoadjuvant setting and you make them sick and they can’t go to surgery because they’re too beat up, the surgeon is going to be very upset, the family is going to be upset, and the patient is going to be upset. So, you have to be careful there.

I just want to comment on the Alliance trial. In the Alliance trial, 15 patients went to surgery and 14 had resections—most of them were portal vein reconstructions, not the tumor unwrapping from the artery. There’s what, 4 hepatic arteries, 12 portal veins? So, as we know, in portal vein reconstruction, there is an issue of your vascular surgeon, or your surgeon, being comfortable reconstructing the vessel. I’m not convinced that FOLFIRINOX is the only regimen for borderline. I think Abraxane-gemcitabine has some good data. The problem is that surgeons love FOLFIRINOX, and they’re the ones that tell us what to give.

Eileen O’Reilly, MD: I think with more data with FOLFIRINOX, as in this setting, most of the big institutions have published their experience. And we had a nice pooled analysis this year, which I thought was pretty reassuring, actually—you know, median survivals approaching 2 years in this patient population. Again, we’re not there, but that’s probably double what we would have come up with a decade ago in the absence of these regimens. Yes, they come at a price, but I think in the right setting with multidisciplinary care and follow-up, I do think the objective of trying to get a patient to surgery is an important one.

John Marshall, MD: Did I say that for the randomized trial that it’s 6 cycles of FOLFIRINOX pre-op?

Eileen O’Reilly, MD: It’s 8 in the chemotherapy.

Johanna Bendell, MD: That’s a lot.

John Marshall, MD: That is a lot.

Caio Max S. Rocha Lima, MD: It’s 7 in the chemotherapy-radiation.

John Marshall, MD: That’s right.

Johanna Bendell, MD: They shortened it.

Caio Max S. Rocha Lima, MD: Because it’s 5 days on the off day—hyperfractionated.

John Marshall, MD: I understand that number and how you get there, but that’s going to be hard to achieve—the thought of getting even more responses after 4 cycles, that kind of thing.

Eileen O’Reilly, MD: The way we think about it is that we review all of these after 4 to 5 cycles. I think the first scan in the metastatic disease, too, undertells the story. And it’s really during the second one that you’re getting a sense of whether the patient’s responding. Even in metastatic disease, where their CN99 is down and they have more liver lesions and they say, “This isn’t right.” And it’s not that uncommon that that scenario is a real one, and you’re trying to rationalize why you’re continuing what you’re doing. But I think their pain is better. And again, that, to me, is where we make the decision—closer to 8 cycles of treatment.

Transcript Edited for Clarity

Transcript:

Johanna Bendell, MD: So, outside of the clinical data, because we’re waiting for the trials to be done, what’s your gestalt, John, on chemotherapy and then on radiation therapy—just completely off of study?

John Marshall, MD: For adjuvant?

Johanna Bendell, MD: For neoadjuvant borderline resectable cancer.

John Marshall, MD: I think the sentiment out there that I can sense is a little bit what Caio was saying. It’s sort of a FOLFIRINOX approach just to see if you can get it down and see if you can convert them. There is this hope and a prayer sense that you can convert them, and I’m not against that approach because we do see, every now and then, dramatic responses. We do in-depth shrinking, local-control kind of approaches. I’ve got patients on both kinds of regimens, but a front-line chemotherapy is appropriate. If they’re still unresectable, I lean toward consolidative radiation at that point. I’m a capecitabine junky. So, I treat my patients with it and then they take that forever.

But that’s my approach, generally. And just because I think the ongoing pressure of systemic chemotherapy is hard to maintain in those patients, where you do still have localized disease, it feels right to me to do radiation in that window. It’s often SBRT (stereotactic body radiation therapy), and it’s a short course. Again, I don’t know that that’s the right thing to do. There’s literature on both sides, but that’s where I am.

Johanna Bendell, MD: That sounds about right. If you don’t get there with chemotherapy, keep pushing the envelope to try to get there. George, do you have a thought on which chemotherapy you would use?

George Kim, MD: In the neoadjuvant setting, I think Abraxane-gemcitabine is very reasonable. There’s good data out there, a high 80% range, where it appears to go on to surgery. If you give somebody FOLFIRINOX in the neoadjuvant setting and you make them sick and they can’t go to surgery because they’re too beat up, the surgeon is going to be very upset, the family is going to be upset, and the patient is going to be upset. So, you have to be careful there.

I just want to comment on the Alliance trial. In the Alliance trial, 15 patients went to surgery and 14 had resections—most of them were portal vein reconstructions, not the tumor unwrapping from the artery. There’s what, 4 hepatic arteries, 12 portal veins? So, as we know, in portal vein reconstruction, there is an issue of your vascular surgeon, or your surgeon, being comfortable reconstructing the vessel. I’m not convinced that FOLFIRINOX is the only regimen for borderline. I think Abraxane-gemcitabine has some good data. The problem is that surgeons love FOLFIRINOX, and they’re the ones that tell us what to give.

Eileen O’Reilly, MD: I think with more data with FOLFIRINOX, as in this setting, most of the big institutions have published their experience. And we had a nice pooled analysis this year, which I thought was pretty reassuring, actually—you know, median survivals approaching 2 years in this patient population. Again, we’re not there, but that’s probably double what we would have come up with a decade ago in the absence of these regimens. Yes, they come at a price, but I think in the right setting with multidisciplinary care and follow-up, I do think the objective of trying to get a patient to surgery is an important one.

John Marshall, MD: Did I say that for the randomized trial that it’s 6 cycles of FOLFIRINOX pre-op?

Eileen O’Reilly, MD: It’s 8 in the chemotherapy.

Johanna Bendell, MD: That’s a lot.

John Marshall, MD: That is a lot.

Caio Max S. Rocha Lima, MD: It’s 7 in the chemotherapy-radiation.

John Marshall, MD: That’s right.

Johanna Bendell, MD: They shortened it.

Caio Max S. Rocha Lima, MD: Because it’s 5 days on the off day—hyperfractionated.

John Marshall, MD: I understand that number and how you get there, but that’s going to be hard to achieve—the thought of getting even more responses after 4 cycles, that kind of thing.

Eileen O’Reilly, MD: The way we think about it is that we review all of these after 4 to 5 cycles. I think the first scan in the metastatic disease, too, undertells the story. And it’s really during the second one that you’re getting a sense of whether the patient’s responding. Even in metastatic disease, where their CN99 is down and they have more liver lesions and they say, “This isn’t right.” And it’s not that uncommon that that scenario is a real one, and you’re trying to rationalize why you’re continuing what you’re doing. But I think their pain is better. And again, that, to me, is where we make the decision—closer to 8 cycles of treatment.